Over the last decade, immunotherapies have revolutionised cancer treatment, where they have demonstrated durable responses in a variety of indications. However, most cancer patients fail to benefit from these treatments and there is an urgent need to both discover new biological pathways and develop novel therapeutics that will unlock the full potential of immunotherapy. Here, we present an overview of how oNKo-Innate aims to reshape the future of immune-oncology. Topics covered include our integrated CRISPR-based target discovery platforms and our active pipeline of innovative therapies that span engineered cytokines, antibodies that unleash immune effector function and a small molecule inhibitor that targets a novel cytokine checkpoint.